In-Planta Metabolism of the Environmentally Persistent Drug Lamotrigine: Detection and Identification of Metabolites

Treated wastewater (TWW) has become an important source of irrigation water. As a result, the agro-environment is continually exposed to pharmaceuticals and personal care products (PPCPs).  One of the environmentally persistent pharmaceutical compounds commonly found in TWW is the anticonvulsant drug lamotrigine (LTG).  LTG is known to be taken up by plant; however, its plant biomass calculation reveals a growing deficit over time, apparently due to its metabolism. Thus, there is a need for understanding the in-planta metabolism of LTG to investigate the metabolites distribution throughout the plant organs and elucidate their structures. In this study, cucumbers plants were exposed to 250 µg L-1 of LTG for 18 days under hydroponic culture. Sixteen metabolites possessing the LTG core structure were detected in plant, several of them in the cucumber fruit. Eight metabolites were identified, among them three were newly discovered. The identification process was mostly based on mass-spectral comparison between the newly discovered metabolite and an in-house synthesized chemical standard. The identified LTG-metabolites were generated by carbamylation, N-glucosidation, -alkylation and -formylation, amidine hydrolysis and N-oxidation. 

This first study on LTG metabolites distribution and their structural elucidation in plant, along with an underway study on their pharmaco-kinetics and quantitative determination will aid to assess the potential health effects and risks on vegetable consumers posed by irrigation with TWW.